Effects of COX-1 or COX-2 Deficiency on Mouse Skin Cancer

用含有v-ras的逆转录病毒转染原代野生型、COX-1-/-和COX-2-/-角化细胞，并将转染后的角化细胞移植到胸腺裸鼠背部。与转染的WT相比，转染的COX-2 -/-角化细胞的肿瘤生长明显降低，而COX-1-/-角化细胞的肿瘤生长仅略有降低。移植了COX-2 -/-角质形成细胞的小鼠的肿瘤发生率也降低了。每平方厘米肿瘤血管数与角化细胞基因型无差异。我们确实观察到，与WT角质形成细胞相比，COX-2 -/-角质形成细胞的增殖率较低，终末分化水平较高，这表明BRDU掺入较低，角蛋白1表达增加。在这种移植模型中，细胞复制水平的降低和终末分化的增加可能是COX-2-/-角质形成细胞产生更少、更小肿瘤的原因。此外，COX-2-/-角化细胞/肿瘤中p-EGFR和p-ERK1/2水平低于野生型角化细胞/肿瘤。

Primary wild type, COX-1-/- and COX-2-/- keraticytes were transfected with a retrovirus containing v-ras and the transfected keratinocytes grafted on to the back of athymic nude mice. Tumor growth from transfected COX-2 -/- keratinocytes was markedly reduced compared to transfected WT, while COX-1-/- keratinocytes showed only slightly reduced tumor growth. Tumor incidence was also reduced in mice grafted with the COX-2 -/- keratinocytes. The number of blood vessels per square cm of tumor did not differ with keratinocyte genotype. We did observe lower proliferation rates and higher levels of terminal differentiation in the COX-2 -/- keratinocytes compared to WT keratinocytes as indicated by lowed BRDU incorporation and increased keratin 1 expression. The lower levels of cell replication and increased terminal differentiation were likely causes of COX-2-/- keratinocytes giving rise to fewer and smaller tumors in this grafting model. In addition, p-EGFR and p-ERK1/2 levels were lower in COX-2-/- keratinocytes/tumors compared to wild type keratinocytes/tumors.